cb9b00724_si_001.pdf (29.45 MB)
Imaging of Tie2 with a Fluorescently Labeled Small Molecule Affinity Ligand
journal contribution
posted on 2019-12-12, 22:30 authored by Peter
David Koch, Maaz S. Ahmed, Rainer H. Kohler, Ran Li, Ralph WeisslederThe receptor tyrosine kinase inhibitor, Tie2, has significant
roles
in endothelial signaling and angiogenesis and is relevant in the pathophysiology
of several diseases. However, there are relatively few small molecule
probes available to study Tie2, making the evaluation of its activity in vivo difficult. Recently, it was discovered that the
small molecule rebastinib (DCC-2036) is a potent Tie2 inhibitor. We
hypothesized that fluorescent derivatives of rebastinib could be used
as imaging agents for Tie2. On the basis of crystallography structures,
we synthesized three fluorescent derivatives, which we then evaluated
in both in vitro and in vivo assays.
We found that the Rebastinib-BODIPY TMR (Reb-TMR) derivative has superior
imaging characteristics in vitro, and we successfully
labeled endothelial cells in vivo. We propose that
this probe could be further used in in vivo applications
for studying the role of Tie2 in disease.